Lymphocytes in the intestine: role and distribution.

Once a pathogen penetrates the surface epithelium, the process of immune activation begins. The pathogen is transported across the intestinal epithelium by M cells and presented to the underlying lymphocytes in Peyer's patches by MHCII positive enterocytes. At the same time, intraepithelial lymphocytes are activated and secrete interferon tau which increases the ability of enterocytes to present antigen. Simultaneously, intraepithelial lymphocytes may also cytolyse pathogens. In Peyer's patches, T-lymphocytes in parafollicular areas interact with antigen presenting cells and antigenic peptides to become activated. B-lymphocytes in follicular areas are also initially activated by the interaction of antigen and their surface Ig. B-lymphocyte activation is enhanced by helper T-lymphocytes so that B-lymphocytes begin to proliferate in germinal centres. Most B-lymphocytes at this stage are surface IgA positive whether induced by T-switch cells or by isotype specific T-lymphocytes. At the same time activated T-suppressor cells and contrasuppressors regulate the immune response to maintain it at an optim level. All these lymphocytes then leave Peyer's patches via blood vessels to mesenteric lymph nodes and the spleen where further cellular activation occurs. Thereafter, activated lymphocytes return to the intestine either directly or via the peripheral circulation. Those that reach the intestine directly, differentiate into effector cells and enter the lamina propria. In the lamina propria, plasma cells and cytotoxic T-lymphocytes destroy pathogens by secreting specific Ig and by cytotoxicity respectively. Activated helper T-lymphocytes in the lamina propria probably help in local responses by acting on the few resting B-lymphocytes present there. T-suppressor lymphocytes enter the epithelium to become intraepithelial lymphocytes and regulate responses by suppressor and contrasuppressor activities. Intraepithelial lymphocytes are also cytotoxic for luminal pathogens. Activated lymphocytes which do not return to the intestine directly enter the thoracic duct and thereby the general circulation. In this way a local gut response is converted into a systemic one and memory lymphocytes are disseminated throughout the body. In addition, suppressor and contrasuppressor T-lymphocytes also become available for peripheral effects. Large number of these lymphocytes remain in circulation, while others return to the intestine to provide local protection. A schematic representation of thetraffic of lymphocytes is shown in Fig. 3.